Polyaromatic amide compounds and pharmaceutical/cosmetic compositions comprised thereof

Novel pharmaceutically/cosmetically-active polyaromatic amides have the structural formula (I): ##STR1## wherein Z is a radical --CO--NH-- or --NH--CO--, and are useful for the treatment of a wide variety of disease states, whether human or veterinary, for example dermatological, rheumatic, respiratory, cardiovascular and ophthalmological disorders, as well as for the treatment of mammalian skin and hair conditions/disorders.

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Claims

1. A polyaromatic amide compound having the structural formula (I): ##STR7## in which Z represents --CO--H-- or --NH--CO--; Ar is a radical having the following formula (a): ##STR8## R.sub.1 is (i) a hydrogen atom, (ii) a radical --CH.sub.3, (iii) a radical --CH.sub.2 --O--R.sub.6, (iv) a radical --O--R.sub.6, (v) a radical --CO--R.sub.7, or (vi) a radical --S(O).sub.t R.sub.9; X is a hydrogen atom or a lower alkyl radical; Y is (i) a radical of the formula; ##STR9## (ii) a radical --CH.sub.2 OR.sub.12, (iii) a radical --COR.sub.13 or (iv) a radical --(CH.sub.2).sub.n --COR.sub.14; R.sub.2 and R.sub.3, which may be identical or different, are each a hydrogen atom, a linear or branched alkyl radical having from 1 to 20 carbon atoms, a radical --OR.sub.6 or a radical --SR.sub.6, and R.sub.2 and R.sub.3 may together form, with the carbon atoms from which they depend, a 5- or 6-membered ring optionally substituted by methyl groups and/or optionally interrupted by an oxygen or sulfur atom; R.sub.4 is a hydrogen atom, a halogen atom, a lower alkyl radical or a radical --OR.sub.6; R.sub.5 has the definition of R.sub.4, and R.sub.4 and R.sub.6 may be identical or different; R.sub.6 is a hydrogen atom, a linear or branched alkyl radical having from 1 to 20 carbon atoms or a radical --CO--R.sub.9 and further wherein the radicals R.sub.6 may be identical or different; R.sub.7 is (a) a hydrogen atom, (b) a lower alkyl radical, (c) a radical of the formula: ##STR10## or (d) a radical --OR.sub.8 wherein R.sub.8 is a hydrogen atom, a linear or branched alkyl radical having from 1 to 20 carbon atoms, an alkenyl radical, a mono- or polyhydroxyalkyl radical, or a phenyl, benzyl or phenethyl radical, which are optionally substituted by at least one halogen atom, or a hydroxyl or nitro functional group; the radicals R.sub.9, which may be identical or different, are each a lower alkyl radical; R.sub.10 is a hydrogen atom or a lower alkyl radical; R.sub.11 is a hydrogen atom, a lower alkyl radical, a radical --CO--R.sub.9 or a radical --COOR.sub.9; R.sub.12 is a radical R.sub.6 or a radical --CH.sub.2 ----O--CH.sub.2 --CH.sub.2 --O--CH.sub.3; R.sub.13 is a hydrogen atom or a lower alkyl radical; R.sub.14 is a radical --OR.sub.8, or a radical of the formula: ##STR11## wherein R' and R", which may be identical or different, are each a hydrogen atom, a lower alkyl radical, a mono- or polyhydroxyalkyl radical, or a phenyl radical optionally substituted by at least one halogen atom, or a hydroxyl or nitro functional group, or R' and R" together with the nitrogen atom attached may form a piperidino, morpholino, pyrrolidino or piperazino radical which are optionally substituted at the 4-position by a C.sub.1 -C.sub.5 alkyl radical or a mono- or polyhydroxyalkyl radical; t is an integer equal to 0, 1 or 2; n is an integer equal to 0 or 1; and the radicals X and Y may together form a double bond-containing single radical of the formula.dbd.N--OR.sub.6 or.dbd.CH--COR.sub.14; or pharmaceutically/cosmetically acceptable salt or optical or geometric isomer thereof.

2. A polyaromatic amide as defined by claim 1, wherein formula (I), Z is the radical --CO--NH--.

3. A polyaromatic amide as defined by claim 1, wherein formula (I), Z is the radical --NH--CO--.

4. A polyaromatic amide as defined by claim 1, comprising a pharmaceutically acceptable salt thereof.

5. A polyaromatic amide as defined by claim 1, wherein formula (I), X is a hydrogen atom, Y is an --NH.sub.2 group, and R.sub.7 is a radical --OR.sub.8.

6. A polyaromatic amide as defined by claim 1, wherein formula (I), the lower alkyl radical substituents are selected from the group consisting of methyl, ethyl, isopropyl, butyl, tert-butyl and hexyl radicals.

7. A polyaromatic amide as defined by claim 1, wherein formula (I), the linear or branched alkyl radical substituents having from 1 to 20 carbon atoms are selected from the group consisting of methyl, ethyl, propyl, 2-ethylhexyl, octyl, dodecyl, hexadecyl and octadecyl radicals.

8. A polyaromatic amide as defined by claim 1, wherein formula (I), the monohydroxyalkyl radical substituents are selected from the group consisting of 2-hydroxypropyl and 3-hydroxypropyl radicals.

9. A polyaromatic amide as defined by claim 1, wherein formula (I), the polyhydroxyalkyl radical substituents are selected from the group consisting of 2,3-dihydroxypropyl, 2,3,4-trihydroxybutyl, 2,3,4,5-tetrahydroxypentyl and pentaerythritol radicals.

10. A polyaromatic amide as defined by claim 1, wherein formula (I), the alkenyl radical substituents have from 1 to 5 carbon atoms and comprise at least one site of ethylenic unsaturation.

11. A polyaromatic amide as defined by claim 1, wherein formula (I), the halogen atom substituents are selected from the group consisting of fluorine, chlorine and bromine atoms.

12. A pharmaceutical composition of matter, comprising a therapeutically effective amount of a polyaromatic amide as defined by claim 1, or pharmaceutically acceptable salt or isomer thereof, and a pharmaceutically acceptable carrier or diluent therefor.

13. The pharmaceutical composition as defined by claim 12, further comprising a retinoid compound, a D vitamin, a corticosteroid, an anti-free radical agent, an.alpha.-hydroxy or.alpha.-keto acid, an ion channel blocker, or combination thereof.

14. The pharmaceutical composition as defined by claim 12, comprising a tablet, a capsule, a syrup, a suspension, an elixir, a solution, a powder, granules, an emulsion, microspheres, nanospheres, lipid vesicles, or polymeric vesicles.

15. The pharmaceutical composition as defined by claim 12, comprising an ointment, a cream, a milk, a pommade, an impregnated pad, a gel, a spray, or a lotion.

16. The pharmaceutical composition as defined by claim 12, which is suitable for topical administration.

17. The pharmaceutical composition as defined by claim 12, which is suitable for systemic administration.

18. The pharmaceutical composition as defined by claim 12, comprising from 0.001% to 5% by weight of said polyaromatic amide, or salt or isomer thereof.

19. A cosmetic composition of matter, comprising a cosmetically effective amount of a polyaromatic amide as defined by claim 1, or cosmetically acceptable salt or isomer thereof, and a cosmetically acceptable carrier or diluent therefor.

20. The cosmetic composition as defined by claim 19, comprising a cream, a milk, a lotion, a gel, microspheres, nanospheres, lipid vesicles, polymeric vesicles, a soap, or a shampoo.

21. The cosmetic composition as defined by claim 19, comprising from 0.001% to 3% by weight of said polyaromatic amide, or salt or isomer thereof.

22. The cosmetic composition as defined by claim 19, further comprising a retinoid compound, a D vitamin, a corticosteroid, an anti-free radical agent, an.alpha.-hydroxy or.alpha.-keto acid, an ion channel blocker, or combination thereof.

23. The pharmaceutical composition as defined by claim 12, further comprising a wetting agent, a depigmenting agent, a moisturizing agent, an antiseborrhoeic or antiacne agent, an antibiotic, an antifungal agent, a hair regrowth promoter, a non-steroidal anti-inflammatory agent, a carotenoid, an anti-psoriatic agent, 5,8,11,14-eicosatetraynoic or 5,8,11-eicosatrynoic acid or ester or amide thereof, or combination thereof.

24. The pharmaceutical composition as defined by claim 12, further comprising a taste- or flavor-enhancing agent, a preservative, a stabilizer, a moisture regulating agent, a pH regulating agent, an osmotic pressure modifying agent, an emulsifying agent, a UV-A or UV-B screening agent, an antioxidant, or combination thereof.

25. The cosmetic composition as defined by claim 19, further comprising a wetting agent, a depigmenting agent, a moisturizing agent, an antiseborrhoeic or antiacne agent, an antibiotic, an antifungal agent, a hair regrowth promoter, a non-steroidal anti-inflammatory agent, a carotenoid, an anti-psoriatic agent, 5,8,11,14-eicosatetraynoic or 5,8,11-eicosatrynoic acid or ester or amide thereof, or combination thereof.

26. The cosmetic composition as defined by claim 19, further comprising a taste- or flavor-enhancing agent, a preservative, a stabilizer, a moisture regulating agent, a pH regulating agent, an osmotic pressure modifying agent, an emulsifying agent, a UV-A or UV-B screening agent, an antioxidant, or combination thereof.

Referenced Cited
U.S. Patent Documents
3829467 August 1974 Diamond et al.
Foreign Patent Documents
0 514 264 November 1992 EPX
92/06948 April 1992 WOX
Patent History
Patent number: 5709867
Type: Grant
Filed: Dec 15, 1994
Date of Patent: Jan 20, 1998
Assignee: Centre International De Recherches Dermatologiques Galderma (Valbonne)
Inventor: Jean-Michel Bernardon (Le Rouret)
Primary Examiner: Jyothsan Venkat
Law Firm: Burns, Doane, Swecker & Mathis, L.L.P.
Application Number: 8/356,680
Classifications
Current U.S. Class: Cosmetic, Antiperspirant, Dentifrice (424/401); Topical Live Body Grooming Or Adorning Aid (e.g., Hair Spray, Antiperspirant, Etc.) (424/47); Carbon Disulfide (424/701); Web, Sheet Or Filament Bases; Compositions Of Bandages; Or Dressings With Incorporated Medicaments (424/443); Liposomes (424/450); 514/2375; 514/255; The Additional Ring Is One Of The Cyclos In A Polycyclo Ring System (514/319); C=x Bonded Directly To The Piperidine Ring (x Is Chalcogen) (514/330); C=x Bonded Directly To The Five-membered Hetero Ring By Nonionic Bonding (x Is Chalcogen) (514/423); Polycyclo Ring System Having The Hetero Ring As One Of The Cyclos (514/434); Polycyclo Ring System Having The Hetero Ring As One Of The Cyclos (514/443); Additional Hetero Ring (514/444); C=o Bonded Directly To The Hetero Ring (x Is Chalcogen) (514/448); Bicyclo Ring System Having The Hetero Ring As One Of The Cyclos (e.g., Chromones, Etc.) (514/456); Bicyclo Ring System Having The Hetero Ring As One Of The Cyclos (514/469); The Nitrogen Of The Z Radical Is Directly Bonded To A Benzene Ring Which Is Directly Bonded To The C(=o) Group (514/535); Rc(=o)n Containing (i.e., Carboxamide) (r Is C Or H) (514/563); Sulfur In R (514/618); Nitrogen In R (514/619); Cosmetic, Facial (514/844); Cleansing Cream Or Lotion (514/846); Ophthalmic (514/912); Veneral Disease (514/931); Gel (514/944); Sulfur Containing Hetero Ring (e.g., Thioxane, Etc.) (544/145); Additional Oxygen Containing Hetero Ring (544/147); Quinoline Or Isoquinoline (including Hydrogenated) (544/363); The Additional Ring Is One Of The Cyclos In A Polycyclo Ring System (546/195); Hetero Ring In The Polycyclo Ring System (546/196); Chalcogen Bonded Directly To Ring Carbon Of The Piperidine Ring (546/242); Chalcogen Bonded Directly To Ring Carbon Of The Six-membered Hetero Ring (546/290); Polycyclo Ring System Which Includes Ring Chalcogen (548/525); Having -c(=x)-, Wherein X Is Chalcogen, Bonded Directly To The Five Membered Hetero Ring (e.g., Pyrrole Carbonyl Halides, Pyrrole Carboxaldehyde, Etc.) (548/530); Nitrogen Attached Indirectly To The Five-membered Hetero Ring By Acyclic Nonionic Bonding (548/566); Chalcogen Attached Indirectly To The Five-membered Hetero Ring By Acyclic Nonionic Bonding (548/570); Polycyclo Ring System Having The Hetero Ring As One Of The Cyclos (549/23); Bicyclo Ring System Having The Hetero Ring As One Of The Cyclos (549/32); Chalcogen Attached Directly To The Bicyclo Ring System By Nonionic Bonding (549/51); Additional Hetero Ring Containing (549/59); The Bicyclo Ring System Consists Of The Hetero Ring And A Six-membered Carbocyclic Ring (549/398); Benzene Ring Bonded Directly To The Hetero Ring (549/469); Nitrogen Attached Indirectly To The Hetero Ring By Nonionic Bonding (549/491); The -c(=x)- Is Part Of A -c(=x)x- Group, Wherein The X's Are The Same Or Diverse Chalcogens (549/499); The Nitrogen Is Not Bonded Directly To A Ring (560/37); Naphthyl In Acid Moiety (560/100); Nitrogen Bonded Directly To Carbon Of Organic Radical (e.g., Amino Acids, Etc.) (562/433); Nitrogen Double Bonded Directly To Carbon (e.g., Amidine, Ketimine, Etc.) (562/440); Sulfur In Substituent Q (564/162); Nitrogen In Substituent Q (564/163); Ring In A Substituent E (564/168); Carbonyl In Substituent Q (564/169)
International Classification: A61K 748;